Qt interval determination methods and related devices

ABSTRACT

Described herein is a system and method of automatically monitoring QT intervals in a patient based on one or more EKG signals received from attached monitoring devices. Each EKG signal is analyzed to detect attributes of the first and second EKG signals, including QRS onset information, QRS peak information, and T-wave offset information. A QT interval is calculated based on QRS onset information derived from the first EKG signal and T-wave offset information derived from the second EKG signal. The calculated QT interval is compared to thresholds to detect elongation of the QT interval and an alert is generated in response to a detected elongated QT interval.

TECHNICAL FIELD

The present disclosure relates to monitoring devices and methods, and inparticularly to devices and methods for determining and monitoring QTintervals in patients.

BACKGROUND

Monitoring of the heart's electrical signals—electrocardiogramsignals—is utilized to monitor the cardiac cycle of patients in order todetect various conditions and disorders. A typical cardiac cycle asrepresented by an electrocardiogram signal (EKG) consists of a P wave, aQRS complex, and a T wave—which appear in that order. An EKG specialistis trained to analyze aspects of the EKG signal to identify potentialdisorders or dangers. The P-wave represents the electrical signalcreated during atrial depolarization; the QRS complex reflects the rapiddepolarization of the right and left ventricles following the atrialdepolarization (P-wave); and the T-wave represents the repolarization orrecovery of the ventricles. The ventricles are larger muscles than theatria, and therefore the depolarization associated with the QRS complexis typically greater in magnitude than the P-wave depolarization orT-wave repolarization. Analysis of the EKG signal includes measurementsrelated to the timing and magnitude of the components of the EKG signal.For example, heart rate is detected based on the interval betweensuccessive peaks of the R portion of the QRS complex (e.g., the R-Rinterval). The PR interval is measured from the beginning of the P waveto the beginning of the QRS complex and reflects the time the electricalimpulse takes to travel from the sinus node through the AV node, andprovides an indication of AV node function. Likewise, the QT interval ismeasured form the beginning of the QRS complex to the end of the T wave.With respect to the measured QT interval, a prolonged QT interval hasbeen identified as a risk factor for a number of conditions, such asacute myocardial infarction and ischemia, hypocalcemia, central nervoussystem events, hypothermia, hypothyroidism, and as a result ofmedication.

In a hospital setting, a 6-lead configuration or 12-lead configurationis typically utilized to collect EKG signals and measure the QTinterval. However, this type of cardiac monitoring typically only takesplace in a hospital for a limited period of time, and typically whilethe patient is non-ambulatory. It would be desirable to providelong-term monitoring (e.g., multiple days) of cardiac activity—and QTinterval detection in particular—in order to detect extreme QT intervalevents that occur infrequently and/or enable the detection of gradualchanges in QT interval. In addition, it would be desirable to monitor apatient's QT interval while the patient is active or engaged inactivities such as standing up or walking around. Finally, it would bebeneficial to be able to monitor and detect a patient's QT intervalwithout the full complement of six or twelve leads typically used forEKG monitoring in a hospital.

SUMMARY

According to one example of the disclosure, a monitoring system thatmeasures QT intervals in patients includes a first monitoring device anda QT interval measurement module. The first monitoring device is adheredto a patient at a first location and monitors a first electrocardiogram(EKG) signal associated with the patient. The QT interval measurementmodule is configured to receive the first EKG signal from the firstmonitoring device, and is configured to identify QRS complex attributesand heart rate attributes for each beat within the received first EKGsignal. Based on identified QRS complex information, the QT intervalmeasurement module locates heart rate attributes a T-wave offset (iToff)for each beat. The QT interval measurement module further selectsqualified beat segments comprised of a plurality of beats suitable forQT interval measurement within the received first EKG signal, andmeasures QT intervals within the qualified beat segments based on QRScomplex attributes and T-wave offsets identified with respect to eachbeat.

According to another example of the disclosure, a monitoring system thatmeasures QT intervals in patients includes first and second monitoringdevices, and a QT interval measurement module. The first monitoringdevice is adhered to a patient at a first location and monitors a firstelectrocardiogram (EKG) signal associated with the patient. The secondmonitoring device is adhered to a patient at a second location differentthan the first location and monitors a second EKG signal associated withthe patient. The QT interval measurement module is configured to receivethe first and second EKG signals from the first and second monitoringdevices, respectively, and identify first attributes associated with thefirst EKG signal and second attributes associated with the second EKGsignal. The QT interval measurement module selects qualified beatsegments comprised of a plurality of beats suitable for QT intervalmeasurement within the received first and second EKG signals, andmeasures QT intervals within the qualified beat segments based on acombination of the first attributes associated with the first EKG signaland second attributes associated with the second EKG signal.

According to another embodiment of the disclosure, a method ofautomatically monitoring QT intervals in a patient includes receivingglobal timing information at a first adherent device and a secondadherent device. The first adherent device measures a firstelectrocardiogram (EKG) signal and associates a timestamp with the firstEKG signal based on received global timing information. The secondadherent device measures a second EKG signal and associates a timestampwith the second EKG signal based on received global timing information.The first and second measured EKG signals and timestamp information iscommunicated from the respective adherent devices to a processor system.A QT interval is calculated based on the first and second EKG signals,wherein the QT interval is calculated based on QRS onset informationderived from the first EKG signal and T-wave offset information derivedfrom the second EKG signal. The calculated QT interval is compared tothresholds to detect elongation of the QT interval and an alert isgenerated in response to a detected elongated QT interval.

According to another embodiment of the disclosure, a method of detectingQT intervals includes receiving a first electrocardiogram (EKG) signalfrom a first device located in a first lead configuration on a patient'sabdomen and receiving a second EKG signal from a second device locatedin a second lead configuration located on the patient's chest at adefined angle relative to the first device. QRS onset and QRS peakinformation are detected with respect to the first EKG signal and QRSpeak and T-wave offset information with respect to the second EKGsignal. A first plurality of beats associated with the first measuredEKG signal are matched with a second plurality of beats associated withthe second EKG signal to align the QRS peaks of the first plurality ofbeats with the QRS peaks of the second plurality of beats. A QT intervalis calculated based on the detected QRS onset information associatedwith the first EKG signal and T-wave offset information associated withthe second EKG signal. Abnormalities in the QT interval are detectedbased on the calculated QT interval.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a schematic view of a monitoring and treatment systemthat measures electrocardiogram signals and performs analysis to measureQT intervals according to an embodiment of the present invention.

FIG. 2 is a graphical representation of an EKG signal that illustratescalculation of the QT interval according to an embodiment of the presentinvention

FIG. 3 is a flowchart that illustrates calculation of the QT intervalbased on a received EKG signal according to an embodiment of the presentinvention.

FIG. 4 illustrates placement of two monitoring devices capable ofmeasuring electrocardiogram (EKG) signals according to an embodiment ofthe present invention.

FIG. 5 is a graphical representation of first and second EKG signalsused to calculate a QT interval according to an embodiment of thepresent invention

FIG. 6 is a flowchart illustrating a method of calculating QT intervalsbased on a two EKG signals received from first and second monitoringdevices, respectively, synchronized in time with one another accordingto an embodiment of the present invention.

FIG. 7 is a flowchart illustrating a method of calculating QT intervalsbased on two EKG signals received from first and second devices,respectively, not synchronized in time with one another according to anembodiment of the present invention.

FIG. 8 is a waveform diagram illustrating matching of first and secondwaveform signals and calculation of QT intervals as a result of thematching according to embodiments of the present invention.

FIGS. 9A-9C are displays illustrating various methods of displayingmeasured QT interval data according to embodiments of the presentinvention.

FIGS. 10A and 10B show an exploded view and a side cross-sectional view,respectively, of adherent devices utilized to measure EKG signalsaccording to embodiments of the present invention.

DETAILED DESCRIPTION

The present invention provides a system and method of measuring the QTinterval and automatically detecting conditions related to the QTinterval such as Long QT Syndrome (LQTS). In one embodiment, a first EKGsignal generated from a first lead configuration (e.g., firstlocation/orientation of an electrocardiogram device) is utilized togather some information related to some aspects of the cardiac cycle(e.g., QRS onset) and a second EKG signal generated from a second leadconfiguration (e.g., second location/orientation of an electrocardiogramdevice) is utilized to gather additional information related to aspectsof the cardiac cycle (e.g., P-wave offset). The first and second EKGsignals are synchronized with one another such that the QT interval maybe measured based on QRS onset information obtained from one EKG signaland T-wave offset information obtained from the other EKG signal. Thecalculated QT interval is then analyzed to detect conditions associatedwith QT interval elongation, including both intermittent events andgradual changes to the QT interval.

FIG. 1 illustrates a schematic view of monitoring and treatment system10 that measures electrocardiogram signals and performs analysis tomeasure QT intervals according to an embodiment of the presentinvention. In the embodiment shown in FIG. 1, monitoring and treatmentsystem 10 includes monitoring device 12, intermediate/QT intervalmeasurement module 14, and remote monitoring system 16. Intermediate/QTinterval measurement module 14 includes antenna 20, micro-processor 22,and storage medium 24. In one embodiment, intermediate device 14 isresponsible for processing EKG signals received from monitoring device12 to measure the QT interval associated with the patient, andreport/alert detected problems to medical personnel at remote monitoringsystem 16. However, in other embodiments, intermediate device 14 issimply an intermediary between monitoring device 12 and remotemonitoring system 16, wherein processing of the EKG signals is performedeither locally at monitoring device 12 or remotely at remote monitoringsystem 16. Remote monitoring system 16 includes micro-processor 28,storage medium 30, and display 32.

Monitoring device 12 is adhered, attached, or otherwise placed in aposition to monitor electrocardiogram signals in patient P. Anembodiment of one such monitoring device is shown in FIGS. 10a-10b . Insome embodiment, monitoring device 12 includes a local processor (notshown) capable of analyzing sensed EKG signal, while in otherembodiments monitoring device 12 maintains a local processor/controllercapable only of communicating measured EKG signals to intermediatedevice 14 or remote monitoring system 16 for further processing and/oranalysis.

In one embodiment, first and second EKG signals are utilized inconjunction with one another to measure the QT interval. The first EKGsignal is measured by monitoring device 12 at a first location—such asthat shown in FIG. 1—and the second EKG signal is measured by monitoringdevice 12 at a second location. For example, in one embodiment the firstlocation is located on patient P's abdomen at an angle approximatelyparallel with the horizon, and the second location is located on patientP's chest at an angle of approximately forty-five degrees to thehorizon—as well as forty-five degrees to the orientation of the deviceat the first location. In one embodiment, this requires first and secondmonitoring devices adhered or otherwise connected to patient P. In otherembodiments however, the same device may be utilized at differentinstances in time to capture EKG data from the desired first and secondlead positions.

Communication and processing of EKG signal(s) sensed with respect topatient P will be performed by the QT interval measurement module, butthis module can reside in any device that has access to the measured EKGsignals and has a processor/storage medium for enabling processing ofthe EKG signals. For example, in the embodiment shown in FIG. 1 QTinterval measurement module may be implemented locally at monitoringdevice 12, at intermediate device 14 (as shown in FIG. 1), and/or atremote monitoring system 16. Depending on the application, it may bebeneficial to perform EKG processing locally on processors included aspart of monitoring device 12 and communicate to intermediate device 14and/or remote monitoring system 16 only the processed results (e.g.,measured QT intervals, etc.). In other applications, it may bebeneficial to perform processing of the EKG signal(s) at intermediatedevice 14 and/or remote monitoring system 16. For embodiments in whichprocessing is performed locally, remote monitoring device 12 includes aprocessor, storage medium and communication interface (shown in moredetail in FIGS. 10a-10b ). Monitored EKG signals are processed locallyby the processor, with results stored to the storage medium orcommunicated via the communication interface to intermediate device 14.In embodiments in which two monitoring device are affixed to patient P,the monitoring devices may be configured to communicate measured EKGsignals to one another for local processing of the EKG signals prior tocommunication to intermediate device 14. In still other embodiments,monitored EKG signals are communicated directly (e.g., unprocessed) tointermediate device 14.

In the embodiment shown in FIG. 1, intermediate device 14 includesantenna 20, processor 22 and storage medium 24. Antenna 20 is configuredto communicate wirelessly with monitoring device 12 via wirelesscommunication path 18, and may include bi-directional communication. Forexample, as discussed in more detail below, in one embodimentintermediate device 14 provides timing signals to monitoring device 12(as well as a second monitoring device) that allows the monitored EKGsignals provided by the respective monitoring devices to be alignedbased on timestamps provided by the timing signals. In addition,monitoring device 12 provides EKG signals and/or processed data tointermediate device 14 via antenna 20. Upon reception, processor 22 andstorage medium 24 may provide processing of the received EKG data and/orfurther processing of processed data received from monitoring device 12.In turn, intermediate device 14 communicates EKG signals, processeddata, and/or alerts to remote monitoring system 16.

Remote monitoring system 16 is connected to communicate via either wiredor wireless communication channel 26 with intermediate device 14. In theembodiment shown in FIG. 1, remote monitoring system includes processor28, storage medium 30 and display 32. As discussed above, processing ofmonitored EKG signals may be performed locally by monitoring device 12,by intermediate device 14, or remotely by remote monitoring system 16.If done remotely at remote monitoring system 16, then EKG signalsmonitored by monitoring device 12 are communicated to remote monitoringsystem 16 via intermediate device 14. Processor 28 and storage medium 30operate in conjunction to process the received EKG signals to detectattributes such as QT interval. Results of the analysis performed canthen be displayed to a user or medical personnel via display 32.

FIG. 2 is a graphical representation of an EKG signal that illustratescalculation of the QT interval according to an embodiment of the presentinvention. In the embodiment shown in FIG. 2, the EKG signal measured bymonitoring device 12 (shown in FIG. 1) consists of three components orphases: the P-wave; the QRS complex (which is comprised of a Q-wave, anR-wave, and an S-wave); and the T-wave. The QT interval is measured fromthe onset of the QRS complex to the end of the T-wave. Accuratemeasurement of the QT interval therefore depends on accurately detectingthe various components of the EKG signal and in particular inidentifying the onset of the QRS complex and the end of the T-wave.

FIG. 3 is a flowchart that illustrates steps performed in measuring theQT interval associated with a particular patient. Steps described withrespect to method 40 may be performed at a single location (e.g.,monitoring device 12, intermediate device 14, or remote monitoringstation 16) or may be split between a plurality of locations with somesteps being performed by monitoring device 12, while others areperformed by intermediate device 14 and/or remote monitoring system 16.

At step 42, an EKG signal is received for analysis. The EKG signal iscomprised of a plurality of cardiac cycles, each cycle comprised of theP-wave, QRS complex, and T-wave components discussed above. At step 44,QRS locations of the EKG signal are identified, including the peak ofthe QRS complex (iRpk) and the QRS onset (iRon). In addition, at step 44additional aspects or attributes associated with the EKG signal may bedetermined, such as heart rate (R-R) of the patient calculated based onthe intervals between the detected QRS peaks and noise values. For eachof the beats identified as comprising a large noise component, abeat-wise noise flag may be set that indicates analysis cannot beconducted on the identified heartbeat or cycle. Components of the EKGsignal detected at step 44 are stored or otherwise retained for use insubsequent steps.

At step 46, the T-wave offset (iToff) is located for each cardiac cycleor beat based on the QRS complex aspects identified at step 42. A numberof algorithms may be utilized to detect the T-wave within an EKG signal,and in particular the T-wave offset value (iToff). In one embodiment,this includes generating a T-wave offset estimate (iToff_estimate) basedon a look-up table that utilizes the measured heart rate valuedetermined at step 44. As the name implies, the T-wave offset estimateiToff_estimate is an estimate of where the T-wave offset is likely to belocated based on the patient's heart rate. The faster the heart rate ofthe patient, the closer the T-wave offset is likely to be located to theQRS peak. The T-wave offset estimate iToff_estimate is used to define aT-wave offset detection window that represents the window of timewherein subsequent analysis will be performed to locate the actualT-wave offset iToff. In one embodiment, the T-wave offset detectionwindow is defined as between the T-wave offset estimate iToff_estimateplus 50 milliseconds (ms). Within the T-wave offset detection window,peak and valley (maximum and minimum values) are located, with thevalley representing the T-wave offset iToff. Depending on the locationand orientation of the monitoring device, in some embodiments the T-waveoffset iToff may be inverted. However, this can be overcome by utilizingthe absolute values of the calculated peak and valleys and/or utilizingaccelerometer values to determine the orientation of the monitoringdevice and whether values need to be inverted as a result. If the T-waveoffset iToff cannot be detected, then a T-wave offset value is notasserted for that beat and it is discarded for analysis purposes.

At step 48, qualified beats within the EKG signal are identified thatare appropriate for QT interval analysis. In one embodiment, this meansanalysis of beats to identify beats that are non-noisy. In thisembodiment, beat-wise noise flags identified at step 44 are utilized todetermine whether a particular segment is noisy or not. In oneembodiment, a segment is identified as non-noisy if a requisite numberof consecutive beats are identified as non-noisy. For example, in oneembodiment, a segment is identified as non-noisy if five or moreconsecutive beats are identified as non-noisy (e.g., no beat-wise noiseflags set). In other embodiments, other thresholds may be utilized todetermine whether a segment is noisy and other criterion may be utilizedto determine whether a segment of groups is well-suited to QT intervalanalysis, such as time of day, activity level of the patient,orientation of the patient, heart rate of the patient, etc.

At step 50, a QT interval is measured with respect to one or more beatswithin identified qualified (e.g., non-noisy) segments. Measurement ofthe QT interval may include measurement of two or more QT intervalsassociated with two or more beats within the qualified segment andaveraging of the measured QT intervals, or measurement of a single QTinterval within the qualified segment. In one embodiment, in addition toidentifying qualified segments, additional requirements are imposed whenmeasuring a QT interval associated with a particular beat. For example,in one embodiment QT intervals are only measured for beats that arepreceded by a non-noisy beat. As a result, the first beat identified ina non-noisy segment—if preceded by a noisy beat—will not be utilized tomeasure a QT interval.

As discussed above, the QT interval is measured from the onset of theQRS complex to the offset or end of the T-wave (e.g., iQT=iToff−iRon).In one embodiment, an additional requirement on whether a QT interval ismeasured for a particular beat is whether attributes of the beatrequired to measure the QT interval—namely the onset of the QRS complexand end of the T-wave—are detectable or otherwise distinguishable in themonitored EKG signal. If these attributes cannot be discerned from theEKG signal, even if found in a non-noisy segment and meeting the otherrequirements, the beat is discarded and not used for measurement of theQT interval.

At step 52, the measured QT interval is corrected based on the heartrate of the patient. A number of well-known algorithms may be utilizedto correct the measured QT interval, including for example thosedeveloped by Bazett, Fridericia, and Framingham, reproduced below:

QTc _(Bazett) =QT/RR ^(0.5)

QTc _(Fridericia) =QT/RR ^(0.33)

QTc _(Framingh) =QT+1.54*(1−RR)

In one embodiment, if more than one corrected QT interval is calculatedfor a measured QT interval, the corrected QT intervals are averagedtogether to provide an averaged calculated QT interval. In someembodiments, a plurality of QT intervals are measured, and for eachmeasured QT interval a corrected QT interval is calculated, resulting ina plurality of corrected QT intervals provided for analysis at step 54.

At step 54, the corrected QT interval(s) are analyzed to detectconditions such as Long QT Syndrome (LQTS). In the simplest embodiment,all corrected QT intervals are utilized in the analysis. In otherembodiments, filters may be utilized to select particular corrected QTintervals for analysis based on one or more other physiologicalparameters of the patient, such as instantaneous heart rate, averageheart rate, activity level of the patient, ongoing arrhythmiainformation, etc.

Analysis of the corrected QT interval may include—in the simplestembodiment—a comparison of the corrected QT interval to a thresholdvalue. If the corrected QT interval is greater than the threshold value,this is indicative of a possible LQTS condition and may result in a flagbeing set or notification sent to attending medical personnel. In otherembodiments, additional physiological parameters or conditions areaccounted for in analyzing the corrected QT interval.

In this way, EKG signals monitored by an adherent device can beautomatically analyzed to detect conditions related to the QT interval.One benefit of this arrangement is that monitoring may occur overseveral days or weeks, with QT intervals (and corrected QT intervals)being calculated and monitored over this time period. This allows notonly for detection of extreme QT interval events that occur infrequentlyand may not be detected in a shorter duration monitoring period, butalso allows for monitoring of trends in the change of the monitored QTinterval over a period of time. In addition, the described system allowsthe patient's QT interval to be monitored during different physiologicalstates, such as while active.

FIG. 4 illustrates placement of monitoring devices 12 a and 12 b onpatient P according to embodiments of the present invention. In contrastwith the embodiments described with respect to FIGS. 2-3, in which theQT interval is determined based on measurements received from a singlemonitoring device—selectively located on one portion of the patient'sbody—the embodiments described with respect to FIGS. 4-5 rely on atleast two EKG signals measured by a monitoring device or devices atdifferent locations. As described in more detail below, one benefit ofutilizing two EKG signals measured at different locations is that eachEKG signal has different attributes (e.g., clearly defined QRS onsetinformation) that when combined allow the QT interval to be accuratelydetermined. In addition, movement of monitoring device or devices—and asa result, movement of associated electrodes—can negatively impact thequality of EKG signals monitored. This issue is particularly problematicwith monitoring of a patient outside of a hospital setting in which thepatient is performing daily activities. Movement of the monitoringdevice and associated electrodes results in noise and/or movementartifacts being introduced into the EKG signals. A benefit of utilizingmore than one monitoring device is that the noise signals associatedwith multiple EKG signals—which are independent of one another—will tendto average out over time.

In the embodiment shown in FIG. 4, first monitoring device 12 a isplaced on the abdomen of patient P while second monitoring device 12 bis placed on the chest of patient P. First monitoring device 12 a isoriented in a horizontal direction—as indicated by the direction of thearrow adjacent to monitoring device 12 a. The position of monitoringdevice 12 a is referred to as a first lead position and generates inresponse a first EKG signal EKG_a. Second monitoring device 12 b islocated on the chest of patient P and oriented at an angle ofapproximately 45 degrees to monitoring device 12 a. The position ofmonitoring device 12 b is referred to as a second lead position andgenerates in response a second EKG signal EKG_b. In one embodiment,first and second monitoring devices 12 a and 12 b are adhered to patientP at approximately the same time, and collect data simultaneously fromthe patient. However, in other embodiments, first and second monitoringdevices may be adhered to patient P at times that only partially overlapwith one another. In still other embodiments, a single monitoring device12 may be placed at the first lead position for a first period of timeand then moved to the second lead position for a second period of time.Similarly, first monitoring device 12 a may be located at first leadposition for a first period of time and then a second monitoring device12 b may be located at second lead position at a second period of timedifferent from and not co-extensive with the first period of time. Ineach of these embodiments however, first and second EKG signals aremeasured from at least first and second locations. This is in contrastwith the embodiments described with respect to FIGS. 2 and 3, in whichan EKG signal measured from a single location is used to detect the QTinterval. Although reference is made throughout with respect to the EKGsignals monitored at the positions illustrated in FIG. 4, monitoringdevices 12 a and 12 b may be located in other positions on patient P.

FIG. 5 illustrates calculation of the QT interval according to anembodiment of the present invention in which first and second EKGsignals are utilized in combination with one another. In the embodimentshown in FIG. 3, monitoring device 12 b located on the patient's chestprovides the EKG signal labeled EKG_b, illustrated in the top portion ofFIG. 5. Monitoring device 12 a located on the patient's abdomen providesthe EKG signal labeled EKG_a, illustrated in the bottom portion of FIG.5.

Although both monitoring devices 12 a and 12 b are monitoring the samecardiac cycle, the difference in location and orientation provides adifferent “view” of that cardiac activity which is reflected in therespective EKG signals of each. For example, with respect to second EKGsignal EKG_b, the onset of the QRS complex is not easily distinguishedor detectable, but the end of the T-wave signal is well distinguished.In contrast, with respect to the first EKG signal EKG_a, the onset ofthe QRS complex is well distinguished, but the end of the T-wave signalis less distinguished. Because the QT interval is measured as theinterval of time between the onset of the QRS complex and the end oroffset of the T-wave, it is important to accurately distinguish anddetect both the onset of the QRS complex and the end of the T-wave. Tothis end, the present invention utilizes characteristics of both thefirst EKG signal EKG_a and the second EKG signal EKG_b in order toaccurately measure the QT interval.

In the embodiment shown in FIG. 5, the QT interval is determined bymeasuring the interval of time between the peak of the QRS complex(iRpk_b) and the end of the T-wave (iToff_b) associated with the secondEKG signal EKG_b as well as the interval of time between the onset ofthe QRS complex (iRon_a) and the peak of the QRS complex (iRpk_a)associated with the first EKG signal. The interval between the peak ofthe QRS complex and the end of the T-wave associated with the second EKGsignal is illustrated graphically in the top waveform of FIG. 3, and canbe expressed as interval_b=iToff_(b)−iRpk_b. The interval between theonset of the QRS complex and the peak of the QRS complex associated withthe first EKG signal is illustrated graphically in the bottom waveformof FIG. 3, and can be expressed as: interval_a=iRpk_a−iRon_a. The QTinterval is defined as the sum of the first and second intervals, whichcan be expressed as: iQT=interval_a+interval_b.

The common denominator in the measured intervals combined to form the QTinterval is the measured peak of the QRS complex of the first and secondEKG signals. For this reason, it is important that the measured QRSpeaks of the first and second EKG signals are aligned with one another.In embodiments in which monitoring devices 12 a and 12 b receive timinginformation from a timing server (e.g., intermediate device 14), therespective first and second EKG signals will have globally synchronizedtime-stamps that do not require additional alignment of the QRS peaks.However, if the monitoring devices are not synchronized via a globaltiming signal, then alignment between the first and second EKG signalscan be verified by detecting the interval between the respective peaksand comparing the detected interval to a threshold value. In theembodiment shown in FIG. 5, this alignment check is illustratedgraphically by the interval between the respective peaks and can beexpressed as: iRpk_(b)−iRpk_(a)<threshold. If the difference in QRS peakvalues is greater than the threshold value, this indicates that the QRSpeaks are not well aligned and therefore that the calculated QT intervalmay be inaccurate as a result. In one embodiment, if the intervalbetween the respective peaks is greater than the threshold value, thecalculated QT interval is discarded as inaccurate. In anotherembodiment, if the interval between the respective peaks is greater thanthe threshold value, the calculated QT interval is modified to accountfor the interval between the respective peaks. For example, the intervalbetween the respective peaks (i.e., iRpk_b−iRpk_a) can be subtractedfrom the calculated QT interval, with the result representing the new QTinterval. Because the QT interval is related to the heart rate of thepatient, in one embodiment it is further required that two or more QRSpeaks be aligned with one another to calculate a QT interval. Thisrequirement ensures that underlying heart rates associated with thefirst and second EKG signals are approximately equal to one another, andas result the effect of heart rate on the QT intervals associated witheach EKG signal will be the same. This requirement is particularlyimportant for comparison of EKG signals not measured at the same time,but for which QRS peaks have been aligned for purposes of measuring QTintervals.

FIG. 6 is a flowchart illustrating a method of calculating QT intervalsbased on a two or more EKG signal received from monitoring devicesaccording to an embodiment of the present invention. In particular, inthe embodiment shown in FIG. 6, global timing information is provided byintermediate device 14 (shown in FIG. 1) or some other device thatallows global time stamps to be associated with both the first EKGsignal EKG_a and the second EKG signal EKG_b. As a result, the methoddescribed with respect to FIG. 6 does not require additional steps toalign the peaks of the QRS complexes, but can instead rely on the globaltime-stamps to align the first and second EKG signals EKG_a and EKG_b.

At step 62, first and second EKG signals EKG_a and EKG_b are receivedfor analysis. Each EKG signal is comprised of a plurality of cardiaccycles, each cycle comprised of the P-wave, QRS complex, and T-wavecomponents discussed with respect to FIG. 2 above. At step 64, QRS andT-wave locations of the EKG signal are identified, including the peak ofthe QRS complex (iRpk), the QRS onset (iRon), and the T-wave offset(iToff). Although grouped with identification of the QRS onset and peak,identification of the T-wave offset (iToff) may include steps describedwith respect to FIG. 3, in which a T-wave offset estimate(iToff_estimate) is selected from a look-up table based on the patient'sheart rate. The T-wave offset estimate iToff_estimate is used to definea T-wave offset detection window that represents the window of timewherein subsequent analysis will be performed to locate the actualT-wave offset iToff. Within the T-wave offset detection window, peak andvalley (maximum and minimum values) are located, and depending onmorphology the T-wave offset iToff is detected.

In addition to these attributes, additional attributes associated witheach EKG signal may be detected at step 64 including heart rate (R-R)and noise values (e.g., beat-wise noise flags). Monitored attributes ofthe EKG signal detected at step 64 are stored or otherwise retained foruse in subsequent steps.

At step 66, beats within the first and second EKG signals are analyzedto select qualified beats (e.g., beats suitable for subsequent analysisof QT intervals). For example, in one embodiment beats are analyzed toidentify non-noisy segments. As discussed above with respect to FIG. 3,beat-wise noise flags are utilized to determine whether a particularsegment is noisy or not. A segment can be identified as non-noisy if arequisite number of consecutive beats are identified as non-noisy. Forexample, in one embodiment, a segment is identified as non-noisy if fiveor more consecutive beats are identified as non-noisy (e.g., nobeat-wise noise flags set). In other embodiments, other thresholds maybe utilized to determine whether a particular segment is noisy or not.In addition to noise levels, identification of qualified beats may alsobe predicated on other monitored parameters associated with patient P,such as time of day measurement are taken, activity level of thepatient, and underlying average heart rate of the patient. For example,in some embodiments it may be desirable to calculate QT intervals duringtimes of patient activity (or conversely, rest).

In one embodiment, a determination of qualified beats performed at step66 requires aligned segments of the first and second EKG signals (EKG_aand EKG_b) to both be qualified (e.g., non-noisy) before a particularsegment is identified as qualified for subsequent analysis. That is, ifa segment of beats associated with the first EKG signal EKG_a isnon-noisy, but the corresponding segment of beats associated with thesecond EKG signal EKG_b (e.g., measured at the same time) are noisy,then at step 66 both segments may be disqualified.

At step 68, QT intervals are measured based on the qualified beatsegments associated with the first and second EKG signals EKG_a andEKG_b. As described in with respect to FIG. 5, measurement of the QTinterval includes measuring a first interval with respect to the firstEKG signal EKG_a, and a second interval with respect to the second EKGsignal EKG_b. The QT interval iQT is represented by the sum of the firstand second intervals. In particular, in the embodiment described withrespect to FIG. 5 the second EKG signal EKG_b is utilized to measure theinterval between the peak of the QRS complex (iRpk_b) and the T-waveoffset (iToff_b). The first EKG signal EKG_a is utilized to measure theinterval between the onset of the QRS complex (iRon_a) and the peak ofthe QRS complex (iRpk_a). The sum of these intervals represents theinterval from the onset of the QRS complex to the offset of the T-wave,which represents the QT interval.

As described with respect to FIG. 3, above, measurement of the QTinterval may include measurement of two or more QT intervals associatedwith two or more beats within a non-noisy segment and averaging of themeasured QT intervals, or measurement of a single QT interval within thenon-noisy segment. Also described with respect to FIG. 3, additionalrequirements may be imposed on which beats within a non-noisy segmentare utilized to measured QT intervals. For example, in one embodiment QTintervals are only measured for beats that are preceded by a non-noisybeat. As a result, the first beat identified in a non-noisy segment—ifpreceded by a noisy beat—will not be utilized to measure a QT interval.In addition, whether a QT interval is measured for a particular beat isfurther predicated on whether the attributes used to calculate theinterval—namely the onset of the QRS complex and end of the T-wave—aredetectable or otherwise distinguishable in the monitored EKG signal. Ifthese attributes cannot be discerned from the EKG signal, even if foundin a non-noisy segment and meeting the other requirements, the beat isdiscarded and not used for measurement of the QT interval.

A benefit of the embodiment described with respect to FIG. 6, is becausethe EKG signals received from the monitoring devices includesynchronized timing information, the respective EKG signals can bealigned based on the timing information and does not require additionalprocessing to align the first and second EKG signals.

At step 70, the measured QT interval or intervals are corrected based onthe heart rate associated with the qualified beats. As described withrespect to FIG. 3, above, a number of well-known algorithms may beutilized to correct the measured QT interval, including for examplethose developed by Bazett, Fridericia, and Framingham. In oneembodiment, if more than one corrected QT interval is calculated for ameasured QT interval, the corrected QT intervals are averaged togetherto provide an averaged calculated QT interval. In some embodiments, aplurality of QT intervals are measured, and for each measured QTinterval a corrected QT interval is calculated, resulting in a pluralityof corrected QT intervals provided for analysis at step 72.

At step 72, the corrected QT interval(s) are analyzed to detectconditions such as Long QT Syndrome (LQTS). In the simplest embodiment,all corrected QT intervals are utilized in the analysis. In otherembodiments, filters may be utilized to select particular corrected QTintervals for analysis based on one or more other physiologicalparameters of the patient, such as instantaneous heart rate, averageheart rate, activity level of the patient, ongoing arrhythmiainformation, etc.

As described with respect to FIG. 3, above, analysis of the corrected QTinterval may include—in the simplest embodiment—a comparison of thecorrected QT interval to a threshold value. If the corrected QT intervalis greater than the threshold value, this is indicative of a possibleLQTS condition and may result in a flag being set or notification sentto attending medical personnel. In other embodiments, additionalphysiological parameters or conditions are accounted for in analyzingthe corrected QT interval.

FIG. 7 is a flowchart illustrating a method of calculating QT intervalsbased on two EKG signals received from a pair of devices that do notshare synchronized global time stamps according to an embodiment of thepresent invention. In contrast with the embodiment described withrespect to FIG. 6, in which time information received by monitoringdevices 12 a and 12 b allowed EKG signals to be aligned based on timesignals, the embodiment described with respect to FIG. 7 allows firstand second EKG signals to be aligned despite the lack of global timinginformation. The EKG signals illustrated graphically with respect toFIG. 5 are referred to again with respect to the embodiment describedwith respect to FIG. 7.

At step 82, first and second EKG signals EKG_a and EKG_b are receivedfor analysis. Each EKG signal is comprised of a plurality of cardiaccycles, each cycle comprised of the P-wave, QRS complex, and T-wavecomponents discussed with respect to FIG. 2 above. At step 84, QRS andT-wave locations of the EKG signal are identified, including the peak ofthe QRS complex (iRpk), the QRS onset (iRon), and the T-wave offset(iToff). Although grouped with identification of the QRS onset and peak,identification of the T-wave offset (iToff) may include steps describedwith respect to FIGS. 3 and 6, in which a T-wave offset estimate(iToff_estimate) is selected from a look-up table based on the patient'sheart rate. The T-wave offset estimate iToff_estimate is used to definea T-wave offset detection window that represents the window of timewherein subsequent analysis will be performed to locate the actualT-wave offset iToff. Within the T-wave offset detection window, peak andvalley (maximum and minimum values) are located, and depending onmorphology the T-wave offset iToff is detected.

In addition to these attributes, additional attributes associated witheach EKG signal may be detected at step 84 including heart rate (R-R)and noise values (e.g., beat-wise noise flags). Monitored attributes ofthe EKG signal detected at step 84 are stored or otherwise retained foruse in subsequent steps.

At step 86, a template signal is selected from the first and second EKGsignals. The selection is arbitrary, and either the first EKG signal orthe second EKG signal may be identified as the template signal. Theremaining EKG signal is identified as the search signal. For thepurposes of this discussion, the first EKG signal EKG_a is identified asthe template signal and the second EKG signal EKG_b is identified as thesearch signal.

At step 88, qualified beats are detected within the template signal(e.g., first EKG signal EKG_a). The criterion for selecting qualifiedone or more qualified segments of beats is similar to that utilized todetect qualified beats described with respect to FIGS. 3 and 5. Inparticular, non-noisy segments are selected based on the beat-wise noiseflags associated with each beat. In addition, heart rate variation ofbeats within a segment may be used as a criterion, wherein segments withlow heart rate variation are desirable. In one embodiment, segments withheart rate variation greater than five beats-per-minute (bpm) arediscarded. This criterion is particularly important when lining upsegments from the first EKG signal and second EKG signal collected ormeasured at different instances of time. Variation in heart rate makesit more difficult to find a matching segment within the search signalthat can be aligned with the template signal.

At step 90, having selected one or more qualified segments of beatswithin the template signal, a matching sequence or segment of beats islocated within the search signal for each template signal segment. Inone embodiment, matches are located based on an algorithm that seeks toalign QRS peaks between the template signal and the search signal.Having identified QRS peak information at step 84 for both the templateand search signals, this information is utilized to match segmentsbetween the template signal and the search signal according to selectedcriterion. For example, in one embodiment a segment is consideredmatching only if the QRS peaks from each are within a certain timeinterval of one another (e.g., 0.01 seconds) and a minimum number of QRSpeaks are aligned with one another (e.g., 60%). Note that alignment ofsegments does not necessarily imply that the respective segments werecollected at the same time. That is, a template signal segment may bealigned with a segment of the search signal measured at a whollydifferent instance in time. Qualifying template string segments based inpart on lack of variation in the heart rate makes it substantiallyeasier to locate matching search string segments. Because the QRS peaksor a substantial number of the QRS peaks between matched segments needto be in alignment, it reasons that the matching segments will sharerelatively similar heart rates.

In one embodiment, the alignment between segments in the template signaland the search signal is generated via an algorithm that selectssuitable segments of beats (e.g., non-noisy) within the search single,and locates a best fit match within the template signal that satisfiesthe defined criterion. In some embodiments, no such match is located andthe search signal segment is discarded so that another search signalsegment can be tested. Various algorithms may be utilized to dynamicallylocate this best between the search signal segment and the templatesignal segment. For example, in one embodiment a b×b beat-lining upprocedure is utilized that is given criterion described above (e.g.,threshold of time between aligned QRS peaks, and percentage of peaksthat need aligning) as input to find matches between the template signaland the search signal. The Needleman/Wunsch algorithm—originallydesigned to align protein or nucleotide sequences—may also be utilizedto locate alignments between the respective template and search signals.In another embodiment, cross-correlation between the template and searchsignal may be utilized to align segments between the respective signals.The cross-correlation approach relies on variation in the templatesignal segment to locate matching segments in the search signalsegments, and therefore may be more well-suited to instances in whichthe patient's heart rate is varying within a wider range.

At step 92, QT intervals are measured based on the aligned beat segmentsselected from the template signal and the search signal (e.g., first andsecond EKG signals EKG_a and EKG_b). Once aligned beat segments havebeen located, calculation of the QT interval proceeds as described withrespect to the embodiment in FIG. 5. Measurement of the QT intervalincludes measuring a first interval with respect to the first EKG signalEKG_a, and a second interval with respect to the second EKG signalEKG_b. The QT interval iQT is represented by the sum of the first andsecond intervals. In particular, in the embodiment described withrespect to FIG. 5 the second EKG signal EKG_b is utilized to measure theinterval between the peak of the QRS complex (iRpk_b) and the T-waveoffset (iToff_b). The first EKG signal EKG_a is utilized to measure theinterval between the onset of the QRS complex (iRon_a) and the peak ofthe QRS complex (iRpk_a). The sum of these intervals represents theinterval from the onset of the QRS complex to the offset of the T-wave,which represents the QT interval.

As described with respect to FIGS. 3 and 5, above, measurement of the QTinterval may include measurement of two or more QT intervals associatedwith two or more beats within a non-noisy segment and averaging of themeasured QT intervals, or measurement of a single QT interval within thenon-noisy segment. Also described with respect to FIGS. 3 and 5,additional requirements may be imposed on which beats within a non-noisysegment are utilized to measured QT intervals. For example, in oneembodiment QT intervals are only measured for beats that are preceded bya non-noisy beat. As a result, the first beat identified in a non-noisysegment—if preceded by a noisy beat—will not be utilized to measure a QTinterval. In addition, whether a QT interval is measured for aparticular beat is further predicated on whether the attributes used tocalculate the interval—namely the onset of the QRS complex and end ofthe T-wave—are detectable or otherwise distinguishable in the monitoredEKG signal. If these attributes cannot be discerned from the EKG signal,even if found in a non-noisy segment and meeting the other requirements,the beat is discarded and not used for measurement of the QT interval.

A benefit of the embodiment described with respect to FIG. 7, is that itmay utilize EKG signals received from monitoring devices that are notsynchronized with one another. As a result, monitoring devices 12 a and12 b do not necessarily have to measure the respective EKG signals atthe same time. In fact, in one embodiment a single monitoring device isutilized at two different locations, and matching segments from the EKGsignals measured at each location are utilized to estimate the patient'sQT interval.

At step 94, the measured QT interval or intervals are corrected based onthe heart rate associated with the qualified beats. As described withrespect to FIG. 3, above, a number of well-known algorithms may beutilized to correct the measured QT interval, including for examplethose developed by Bazett, Fridericia, and Framingham. In oneembodiment, if more than one corrected QT interval is calculated for ameasured QT interval, the corrected QT intervals are averaged togetherto provide an averaged calculated QT interval. In some embodiments, aplurality of QT intervals are measured, and for each measured QTinterval a corrected QT interval is calculated, resulting in a pluralityof corrected QT intervals provided for analysis at step 95.

At step 95, the corrected QT interval(s) are analyzed to detectconditions such as Long QT Syndrome (LQTS). In the simplest embodiment,all corrected QT intervals are utilized in the analysis. In otherembodiments, filters may be utilized to select particular corrected QTintervals for analysis based on one or more other physiologicalparameters of the patient, such as instantaneous heart rate, averageheart rate, activity level of the patient, ongoing arrhythmiainformation, etc.

As described with respect to FIG. 3, above, analysis of the corrected QTinterval may include—in the simplest embodiment—a comparison of thecorrected QT interval to a threshold value. If the corrected QT intervalis greater than the threshold value, this is indicative of a possibleLQTS condition and may result in a flag being set or notification sentto attending medical personnel. In other embodiments, additionalphysiological parameters or conditions are accounted for in analyzingthe corrected QT interval.

FIG. 8 is a waveform diagram illustrating matching of first and secondwaveform signals and calculation of QT intervals as a result of thematching according to embodiments of the present invention that utilizea template signal and a search signal to align EKG signals. Inembodiments in which both EKG signals have global timing informationreceived from a timing server (e.g., intermediate device 14 shown inFIG. 1), then alignment of the beats is not required because the timinginformation can be relied upon for this purpose. However, in theembodiment shown in FIG. 8, no timing information is provided andinstead alignment of the beats using a template signal and a searchsignal is required.

In the embodiment shown in FIG. 8, a template signal is illustrated inthe top waveform chart and a search signal is illustrated in the bottomwaveform chart. In the graphical representation of the EKG signals, anumber of cardiac cycles are illustrated and components of each cardiaccycle—including QRS and T-wave components, beat-wise noise flags, heartrate, etc.—are automatically identified. In addition, with respect tothe template signal, qualified beats are detected as illustrated in FIG.8 by beats LB1-LB6. In this embodiment, the prefix “LB” is an acronymfor “lined beats”, and represents those beats that are aligned forpotential QT information extraction. Identification of qualified beatsmay be based on one or more criterion, including identification ofnon-noisy segments based on beat-wise noise flags, and relatively stableheart rate within the identified segment. In addition, other criterionsuch as time of day and/or activity level of the patient may further beutilized to determine whether a segment should utilized for QT intervalanalysis or not.

Having identified a qualified segment of beats (e.g., LB1-LB6) withinthe template signal, a matching sequence of beats is located within thesearch signal. The beats identified within the search signal are notrequired to have been measured contemporaneously with the aligned beatsfrom the template signal, although in some applications it may bedesirable that the aligned beats are selected from time periods ofoverlapping measurement of first and second EKG signals. One or morecriterion may be utilized to determine whether a search signal segmentmatches a template signal segment. For example, as described withrespect to the embodiment shown in FIG. 7, criterion such as a minimumthreshold of time between aligned QRS peaks may be imposed to ensurealignment between the QRS peaks. In addition, criterion may include thata certain percentage of QRS peaks within a given segment must be alignedin order for the segment to qualify as properly aligned. In embodimentsin which the heart rate of the template signal is relatively stable, itwill often result in the search signal segment having a heart raterhythm substantially equal to the heart rate of the template signalsegment. In the embodiment shown in FIG. 8, a plurality of beats withinthe search signal have been aligned with the beats LB1-LB6 within thequalified template segment. In the embodiment shown in FIG. 8, the onsetof QRS complexes within each beat are aligned with one another—asopposed to QRS peaks, which may also be utilized. The difference inlocation and orientation of the monitoring devices utilized to measurethe first and second EKG signal (template and search signals,respectively) causes differences in the shape of the template signal andthe search signal. Once aligned, the QT interval can be measured asdescribed above and utilized to detect conditions such as long QTintervals. Although in order to qualify as aligned, the QRS peaks arethe aligned beats are required to be within a defined threshold of oneanother (e.g., 0.01 seconds), small differences in alignment between therespective QRS peaks such as those shown in FIG. 8 can be accounted forby subtracting the difference in QRS peaks (e.g., iRpk_b−iRpk_a) fromthe measured QT interval.

FIGS. 9A-9C are displays illustrating various methods of displayingmeasured QT interval data according to embodiments of the presentinvention. Collection and display of the information illustrated inFIGS. 9A-9C may be monitored by a caregiver or medical personnel toprovide a quick overview of a patient's condition. In addition to thedata illustrated in FIGS. 9A-9C, more detailed QTc data may be madeavailable to a caregiver or medical personnel along with raw EKGsignals. In addition, it should be noted that displays shown in FIGS.9A-9C are not exhaustive of how corrected QT interval data can bedisplayed.

In the embodiment shown in FIG. 9A, QT interval measurements correctedas described above based on heart rate information (e.g., QTc data) isdisplayed versus time to allow trends in the patient's QT interval to beanalyzed. The length of time may vary depending on the application fromseveral hours to several weeks or more. In the embodiment shown in FIG.9A, QTc data is shown for a seven day period, which measured QT dataincluding a mean QTc value, maximum QTc value, and a minimum QTc value.The information illustrated in FIG. 9A allows a caregiver or medicalpersonnel to quickly determine trends in the patient's QT interval.

In the embodiment shown in FIG. 9B, corrected QT intervals QTc aregrouped into bins and displayed versus time. For example, the exampleshown in FIG. 9B consists of four bins each representing a differentrange of corrected QT intervals. In the embodiment shown in FIG. 9B, thefirst bin is defined as less than 300 milliseconds (ms), the second binis defined as between 300 ms and 400 ms, and third bin is defined asbetween 400 ms and 450 ms, and the fourth bin is defined as greater than450 ms. Each measured QT interval is placed into one of the definedbins, and the graphical display shown in FIG. 9B visually illustratesthe number of measurements collected in each bin. In this way, areviewing caregiver or medical personnel can visually review the numberof QT intervals that are considered out of spec or long. For example, inthe embodiment shown in FIG. 9B, on the October 5^(th) date, a number ofmeasured QT intervals are greater than 450 ms.

In the embodiment shown in FIG. 9C, corrected QT intervals arecorrelated with the patient's activity level. In one embodiment,activity level is determined based on heart rate information, 3Daccelerometer information, activity sensor, or a combination thereof. Inthe embodiment shown in FIG. 9C, activity levels include low activity,sedentary, mild, moderate and heavy. As part of the measuring process, adetermination is made of the patient's current activity level andcorrected QT intervals measured during this time are associated with theidentified activity level. In the embodiment shown in FIG. 9C, both meancorrected QT intervals and maximum corrected QT intervals are displayed.The display shown in FIG. 9C allows a caregiver or medical personnel toquickly review data and detect trends related to activity level of thepatient. It should be noted, that while the QT interval will decrease intime with increasing activity (e.g., increasing heart rate), thecorrected QT interval QTc corrects the measured QT interval based onheart rate, so that measurements taken during heavy activity reflectthis correction of the measured QT interval.

In each of the examples shown in with respect to FIGS. 9A-9C, the goalis provide an output or display that allows a caregiver or medicalpersonnel to quickly identify potentially problematic issues. Inaddition to this type of display, calculated QT intervals (bothcorrected and non-corrected) and measured EKG signals may be providedfor review by the caregiver and/or medical personnel. In one embodiment,the displays shown in FIG. 9A-9C are used as a preliminary review of QTintervals associated with a patient, with additional informationprovided to a caregiver or medical personnel upon request or if athreshold is crossed with respect to the information shown in FIGS.9A-9C.

FIGS. 10A and 10B show an exploded view and a side cross-sectional view,respectively, of adherent devices utilized to measure EKG signalsaccording to embodiments of the present invention. The adherent device100 may comprise an adherent patch 110 with an adhesive 116B, electrodes112A, 112B, 112C, 112D with gels 114A, 114B, 114C, 114D, gel cover 180,temperature sensor 177, cover 162, and a printed circuit board (PCB) 120with various circuitry for monitoring physiological sensors,communicating wirelessly with a remote center, and providing alerts whennecessary. The adherent device 100 comprises at least two electrodes andin the embodiment shown in FIGS. 9A and 9B is comprised of fourelectrodes 112A, 112B, 112C and 112D. Adherent device 100 may comprise amaximum dimension, for example a maximum length from about 4 to 10inches, a maximum thickness along a profile of the device from about 0.2inches to about 0.6 inches, and a maximum width from about 2 to about 4inches.

The adherent patch 110 comprises a first side, or a lower side 110A,that is oriented toward the skin of the patient when placed on thepatient. The adherent patch 110 may also comprise a tape 110T which is amaterial, preferably breathable, with an adhesive 116A to adhere topatient P. Electrodes 112A, 112B, 112C and 112D are affixed to adherentpatch 110. In many embodiments, at least four electrodes are attached tothe patch. Gels 114A, 114B, 114C and 114D can each be positioned overelectrodes 112A, 112B, 112C and 112D, respectively, to provideelectrical conductivity between the electrodes and the skin of thepatient. Adherent patch 100 also comprises a second side, or upper side110B. In many embodiments, electrodes 112A, 112B, 112C and 112D extendfrom lower side 110A through adherent patch 110 to upper side 110B. Anadhesive 116B can be applied to upper side 110B to adhere structures,for example a breathable cover, to the patch such that the patch cansupport the electronics and other structures when the patch is adheredto the patient.

In many embodiments, adherent patch 110 may comprise a layer ofbreathable tape 110T, for example a tricot-knit polyester fabric, toallow moisture vapor and air to circulate to and from the skin of thepatient through the tape. In many embodiments, breathable tape 110Tcomprises a backing material, or backing 111, with an adhesive. In manyembodiments, the backing is conformable and/or flexible, such that thedevice and/or patch do not become detached with body movement. In manyembodiments, the adhesive patch may comprise from 1 to 2 pieces, forexample 1 piece. In many embodiments, adherent patch 110 comprisespharmacological agents, such as at least one of beta blockers, aceinhibiters, diuretics, steroid for inflammation, antibiotic, antifungalagent, and cortisone steroid. Patch 110 may comprise many geometricshapes, for example at least one of oblong, oval, butterfly, dogbone,dumbbell, round, square with rounded corners, rectangular with roundedcorners, or a polygon with rounded corners. In specific embodiments, athickness of adherent patch 110 is within a range from about 0.001″ toabout 0.020″, length of the patch is within a range from about 2″ toabout 10″, and width of the patch is within a range from about 1″ toabout 5″.

In many embodiments, the adherent device 100 comprises a temperaturesensor 177 disposed over a peripheral portion of gel cover 180 to allowthe temperature near the skin to be measured through the breathable tapeand the gel cover. Temperature sensor 177 can be affixed to gel cover180 such that the temperature sensor can move when the gel coverstretches and tape stretch with the skin of the patient. Temperaturesensor 177 may be coupled to temperature sensor circuitry 144 through aflex connection comprising at least one of wires, shielded wires,non-shielded wires, a flex circuit, or a flex PCB. The temperaturesensor can be affixed to the breathable tape, for example through acutout in the gel cover with the temperature sensor positioned away fromthe gel pads. A heat flux sensor can be positioned near the temperaturesensor for example to measure heat flux through to the gel cover.

The adherent device comprises electrodes 112A, 112B, 112C and 112Dconfigured to couple to tissue through apertures in the breathable tape110T. Electrodes 112A, 112B, 112C and 112D can be fabricated in manyways, for example printed on a flexible connector 112F, such as silverink on polyurethane. In some embodiments, the electrodes may comprise atleast one of carbon-filled ABS plastic, Ag/AgCl, silver, nickel, orelectrically conductive acrylic tape. The electrodes may comprise manygeometric shapes to contact the skin, for example at least one ofsquare, circular, oblong, star shaped, polygon shaped, or round. Inspecific embodiments, a dimension across a width of each electrode iswithin a range from about 002″ to about 0.050″. In specific embodiments,the two inside electrodes may comprise force, or current electrodes,with a center to center spacing within a range from about 20 to about 50mm. In specific embodiments, the two outside electrodes may comprisemeasurement electrodes, for example voltage electrodes, and acenter-center spacing between adjacent voltage and current electrodes iswithin a range from about 15 mm to about 35 mm. Therefore, in manyembodiments, a spacing between inner electrodes may be greater than aspacing between an inner electrode and an outer electrode.

In many embodiments, gel 114A, or gel layer, comprises a hydrogel thatis positioned on electrode 112A and provides a conductive interfacebetween skin and electrode, so as to reduce impedance betweenelectrode/skin interface. The gel may comprise water, glycerol, andelectrolytes, pharmacological agents, such as beta blockers, aceinhibiters, diuretics, steroid for inflammation, antibiotic, andantifungal agents. Gels 114A, 114B, 114C and 114D can be positioned overelectrodes 112A, 112B, 112C and 112D, respectively, so as to coupleelectrodes to the skin of the patient. The flexible connector 112Fcomprising the electrodes can extend from under the gel cover to the PCBto connect to the PCB and/or components supported thereon. For example,flexible connector 112F may comprise flexible connector 122A to providestrain relief.

A gel cover 180, or gel cover layer, for example a polyurethanenon-woven tape, can be positioned over patch 110 comprising thebreathable tape to inhibit flow of gels 114A-114D through breathabletape 110T. Gel cover 180 may comprise at least one of a polyurethane,polyethylene, polyolefin, rayon, PVC, silicone, non-woven material,foam, or a film. Gel cover 180 may comprise an adhesive, for example anacrylate pressure sensitive adhesive, to adhere the gel cover toadherent patch 110. In many embodiments, the gel cover can regulatemoisture of the gel near the electrodes so as to keeps excessivemoisture, for example from a patient shower, from penetrating gels nearthe electrodes. A PCB layer, for example the flex PCB 120, or flex PCBlayer, can be positioned over gel cover 180 with electronic components130 connected and/or mounted to the flex PCB 120, for example mounted onflex PCB so as to comprise an electronics layer disposed on the flex PCBlayer. In many embodiments, the gel cover may avoid release of excessivemoisture form the gel, for example toward the electronics and/or PCBmodules. In many embodiments, a thickness of gel cover is within a rangefrom about 0.0005″ to about 0.020″. In many embodiments, gel cover 180can extend outward from about 0-20 mm from an edge of gels. Gel layer180 and breathable tape 110T comprise apertures 180A, 180B, 180C and180D through which electrodes 112A-112D are exposed to gels 114A-114D.

In many embodiments, device 100 includes a printed circuitry, forexample a PCB module that includes at least one PCB with electronicscomponent mounted thereon. The printed circuit may comprise polyesterfilm with silver traces printed thereon. Rigid PCB's 120A, 120B, 120Cand 120D with electronic components may be mounted on the flex PCB 120.In many embodiments, the PCB module comprises two rigid PCB modules withassociated components mounted therein, and the two rigid PCB modules areconnected by flex circuit, for example a flex PCB. In specificembodiments, the PCB module comprises a known rigid FR4 type PCB and aflex PCB comprising known polyimide type PCB. Batteries 150 may bepositioned over the flex PCB and electronic components. Batteries 150may comprise rechargeable batteries that can be removed and/orrecharged. A cover 162 may be placed over the batteries, electroniccomponents and flex PCB. In specific embodiments, the PCB modulecomprises a rigid PCB with flex interconnects to allow the device toflex with patient movement. The geometry of flex PCB module may comprisemany shapes, for example at least one of oblong, oval, butterfly,dogbone, dumbbell, round, square, rectangular with rounded corners, orpolygon with rounded corners. In specific embodiments the geometricshape of the flex PCB module comprises at least one of dogbone ordumbbell. The PCB module may comprise a PCB layer with flex PCB 120 thatcan be positioned over gel cover 180 and electronic components 130connected and/or mounted to flex PCB 120. In many embodiments, theadherent device may comprise a segmented inner component, for examplethe PCB, for limited flexibility.

In many embodiments, an electronics housing 160 encapsulates theelectronics layer. Electronics housing 160 may comprise an encapsulant,such as a dip coating, which may comprise a waterproof material, forexample silicone, epoxy, other adhesives and/or sealants. In manyembodiments, the PCB encapsulant protects the PCB and/or electroniccomponents from moisture and/or mechanical forces. The encapsulant maycomprise silicone, epoxy, other adhesives and/or sealants. In someembodiments, the electronics housing may comprising metal and/or plastichousing and potted with aforementioned sealants and/or adhesives.

In many embodiments, cover 162 can encase the flex PCB, electronics,and/or adherent patch 110 so as to protect at least the electronicscomponents and the PCB. In some embodiments, cover 162 can be adhered toadherent patch 110 with an adhesive 164 or adhesive 116B on an undersideof cover 162. In many embodiments, cover 162 attaches to adherent patch110 with adhesive 116B, and cover 162 is adhered to the PCB module withan adhesive 161 on the upper surface of the electronics housing. Cover162 can comprise many known biocompatible cover materials, for examplesilicone, an outer polymer cover to provide smooth contour withoutlimiting flexibility, a breathable fabric, or a breathable waterresistant cover. In some embodiments, the breathable fabric may comprisepolyester, nylon, polyamide, and/or elastane (Spandex™). Work inrelation to embodiments of the present invention suggests that thesecoatings can be important to keep excessive moisture from the gels nearthe electrodes and to remove moisture from body so as to provide patientcomfort.

In many embodiments, cover 162 can be attached to adherent patch 110with adhesive 116B such that cover 162 stretches and/or retracts whenadherent patch 110 stretches and/or retracts with the skin of thepatient. For example, cover 162 and adherent patch 110 can stretch intwo dimensions along the length and width of the adherent patch with theskin of the patient, and stretching along the length can increasespacing between electrodes. Stretching of the cover and adherent patch110 can extend the time the patch is adhered to the skin as the patchcan move with the skin. Electronics housing 160 can be smooth and allowbreathable cover 162 to slide over electronics housing 160, such thatmotion and/or stretching of cover 162 is slidably coupled with housing160. The PCB can be slidably coupled with adherent patch 110 thatcomprises breathable tape 110T, such that the breathable tape canstretch with the skin of the patient when the breathable tape is adheredto the skin of the patient, for example along two dimensions comprisingthe length and the width.

The breathable cover 162 and adherent patch 110 comprise breathable tapethat can be configured to couple continuously for at least one week theat least one electrode to the skin so as to measure breathing of thepatient. The breathable tape may comprise the stretchable breathablematerial with the adhesive and the breathable cover may comprises astretchable breathable material connected to the breathable tape, asdescribed above, such that both the adherent patch and cover can stretchwith the skin of the patient. Arrows 182 show stretching of adherentpatch 110, and the stretching of adherent patch can be at least twodimensional along the surface of the skin of the patient. As notedabove, connectors 122A-122D between PCB 130 and electrodes 112A-112D maycomprise insulated wires that provide strain relief between the PCB andthe electrodes, such that the electrodes can move with the adherentpatch as the adherent patch comprising breathable tape stretches. Arrows184 show stretching of cover 162, and the stretching of the cover can beat least two dimensional along the surface of the skin of the patient.

The PCB 120 may be adhered to the adherent patch 110 comprisingbreathable tape 110T at a central portion, for example a single centrallocation, such that adherent patch 110 can stretched around this centralregion. The central portion can be sized such that the adherence of thePCB to the breathable tape does not have a substantial effect of themodulus of the composite modulus for the fabric cover, breathable tapeand gel cover, as described above. For example, the central portionadhered to the patch may be less than about 100 mm², for example withdimensions that comprise no more than about 10% of the area of patch110, such that patch 110 can stretch with the skin of the patient.Electronics components 130, PCB 120, and electronics housing 160 arecoupled together and disposed between the stretchable breathablematerial of adherent patch 110 and the stretchable breathable materialof cover 160 so as to allow the adherent patch 110 and cover 160 tostretch together while electronics components 130, PCB 120, andelectronics housing 160 do not stretch substantially, if at all. Thisdecoupling of electronics housing 160, PCB 120 and electronic components130 can allow the adherent patch 110 comprising breathable tape to movewith the skin of the patient, such that the adherent patch can remainadhered to the skin for an extended time of at least one week.

An air gap 169 may extend from adherent patch 110 to the electronicsmodule and/or PCB, so as to provide patient comfort. Air gap 169 allowsadherent patch 110 and breathable tape 110T to remain supple and move,for example bend, with the skin of the patient with minimal flexingand/or bending of PCB 120 and electronic components 130, as indicated byarrows 186. PCB 120 and electronics components 130 that are separatedfrom the breathable tape 110T with air gap 169 can allow the skin torelease moisture as water vapor through the breathable tape, gel cover,and breathable cover. This release of moisture from the skin through theair gap can minimize, and even avoid, excess moisture, for example whenthe patient sweats and/or showers. Gap 169 extends from adherent patch110 to the electronics module and/or PCB a distance within a range fromabout 0.25 mm to about 4 mm.

In many embodiments, the adherent device comprises a patch component andat least one electronics module. The patch component may compriseadherent patch 110 comprising the breathable tape with adhesive coating116A, at least one electrode, for example electrode 112A and gel 114A.The at least one electronics module can be separable from the patchcomponent. In many embodiments, the at least one electronics modulecomprises the flex PCB 120, electronic components 130, electronicshousing 160 and cover 162, such that the flex PCB, electroniccomponents, electronics housing and cover are reusable and/or removablefor recharging and data transfer, for example as described above. Inspecific embodiments, the electronic module can be adhered to the patchcomponent with a releasable connection, for example with Velcro™, aknown hook and loop connection, and/or snap directly to the electrodes.Monitoring with multiple adherent patches for an extended period isdescribed in U.S. Pub. No. 2009-0076345-A1, published on Mar. 19, 2009,the full disclosure of which has been previously incorporated herein byreference, and which adherent patches and methods are suitable forcombination in accordance with embodiments described herein.

The adherent device 100, shown in FIG. 10A, may comprise an X-axis,Y-axis and Z-axis for use in determining the orientation of the adherentdevice 100 and/or the patient P. Electric components 130 may comprise a3D accelerometer. As the accelerometer of adherent device 100 can besensitive to gravity, inclination of the patch relative to an axis ofthe patient can be measured, for example when the patient stands.Vectors from a 3D accelerometer can be used to determine the orientationof a measurement axis of the patch adhered on the patient and can beused to determine the angle of the patient, for example whether thepatient is laying horizontally or standing upright, when measuredrelative to the X-axis, Y-axis and/or X-axis of adherent device 100.

FIG. 10B shows a PCB and electronic components over adherent patch 110.In some embodiments, PCB 120, for example a flex PCB, may be connectedto electrodes 112A, 112B, 112C and 112D of FIG. 10B with connectors122A, 122B, 122C and 122D, respectively, and may include traces 123A,123B, 123C and 123D that extend to connectors 122A, 122B, 122C and 122D.In some embodiments, connectors 122A-122D may comprise insulated wiresand/or a film with conductive ink that provide strain relief between thePCB and the electrodes.

Electronic components 130 comprise components to take physiologicmeasurements, transmit data to intermediate device 14 (shown in FIG. 1)and receive commands and/or timing signals from intermediate device 14.In many embodiments, electronics components 130 may comprise known lowpower circuitry, for example complementary metal oxide semiconductor(CMOS) circuitry components. Electronics components 130 comprise atemperature sensor, an activity sensor and activity circuitry 134,impedance circuitry 136 and electrocardiogram circuitry, for example ECGcircuitry 138. In some embodiments, electronic circuitry 130 maycomprise a microphone and microphone circuitry 142 to detect an audiosignal, such as heart or respiratory sound, from within the patient.

Activity sensor and activity circuitry 134 can comprise many knownactivity sensors and circuitry. In many embodiments, the accelerometercomprises at least one of a piezoelectric accelerometer, capacitiveaccelerometer or electromechanical accelerometer. The accelerometer cancomprise a 3-axis accelerometer to measure at least one of aninclination, a position, an orientation or acceleration of the patientin three dimensions. Work in relation to embodiments of the presentinvention suggests that three dimensional orientation of the patient andassociated positions, for example sitting, standing, lying down, can bevery useful when combined with data from other sensors, for examplehydration data. In addition, impedance circuitry 136 can generate bothhydration data and respiration data. These physiological parameters canbe utilized in conjunction with the measured EKG signals to determinewhether or not segments of beats should be analyzed for conditions suchas long QT syndrome, and may be used in conjunction with measured QTintervals to diagnose underlying conditions.

In many embodiments, impedance circuitry 136 is electrically connectedto electrodes 112A, 112B, 112C and 112D of FIG. 10A in a four poleconfiguration, such that electrodes 112A and 112D comprise outerelectrodes that are driven with a current and comprise force electrodesthat force the current through the tissue. The current delivered betweenelectrodes 112A and 112D generates a measurable voltage betweenelectrodes 112B and 112C, such that electrodes 112B and 112C compriseinner, sense, electrodes that sense and/or measure the voltage inresponse to the current from the force electrodes. In some embodiments,electrodes 112B and 112C may comprise force electrodes and electrodes112A and 112D may comprise sense electrodes. The voltage measured by thesense electrodes can be used to measure the impedance of the patient anddetermine the respiration rate and/or hydration of the patient. In manyembodiments, impedance circuitry 136 can be configured to determinerespiration of the patient. In specific embodiments, the impedancecircuitry can measure the hydration at 25 Hz intervals, for example at25 Hz intervals using impedance measurements with a frequency from about0.5 kHz to about 20 kHz.

ECG circuitry 138 can generate electrocardiogram signals and data fromtwo or more of electrodes 112A, 112B, 112C and 112D in many ways. Insome embodiments, ECG circuitry 138 is connected to inner electrodes112B and 122C, which may comprise sense electrodes of the impedancecircuitry as described above. In many embodiments, the ECG circuitry maymeasure the ECG signal from electrodes 112A and 112D when current is notpassed through electrodes 112A and 112D.

Electronic circuitry 130 may comprise a processor 146 that can beconfigured to control a collection, analysis and/or transmission of datafrom the impedance circuitry electrocardiogram circuitry and theaccelerometer. Processor 146 comprises a tangible medium, for exampleread only memory (ROM), electrically erasable programmable read onlymemory (EEPROM) and/or random access memory (RAM). Electronic circuitry130 may comprise real time clock and frequency generator circuitry 148.In some embodiments, processor 146 may comprise the frequency generatorand real time clock. In many embodiments, device 100 comprises adistributed processor system, for example with multiple processors ondevice 100.

In many embodiments, electronics components 130 comprise wirelesscommunications circuitry 132 to communicate with intermediate device 14(shown in FIG. 1). PCB 120 may comprise an antenna to facilitatewireless communication. The antenna may be integral with PCB 120 or maybe separately coupled thereto. The wireless communication circuitry canbe coupled to the impedance circuitry, the electrocardiogram circuitryand the accelerometer to transmit to a remote center with acommunication protocol at least one of the hydration signal, theelectrocardiogram (EKG) signal or the activity/inclination signal. Inspecific embodiments, wireless communication circuitry 132 is configuredto transmit the hydration signal, the electrocardiogram signal and theinclination signal to the remote monitoring system 16 (shown in FIG. 1)either directly or through intermediate device 14 (also shown in FIG.1). The communication protocol comprises at least one of Bluetooth,ZigBee, WiFi, WiMAX, IR, amplitude modulation or frequency modulation.In many embodiments, the communications protocol comprises a two wayprotocol such that the remote center is capable of issuing commands tocontrol data collection.

In many embodiments, the electrodes are connected to the PCB with a flexconnection, for example trace 123A, 123B, 123C and 123D of flex PCB 120,so as to provide strain relief between the electrodes 112A, 112B, 112Cand 112D and the PCB. In such embodiments, motion of the electrodesrelative to the electronics modules, for example rigid PCB's 120A, 120B,120C and 120D with the electronic components mounted thereon, does notcompromise integrity of the electrode/hydrogel/skin contact. In manyembodiments, the flex connection comprises at least one of wires,shielded wires, non-shielded wires, a flex circuit, or a flex PCB. Inspecific embodiments, the flex connection may comprise insulated,non-shielded wires with loops to allow independent motion of the PCBmodule relative to the electrodes.

While the invention has been described with reference to an exemplaryembodiment(s), it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particular situationor material to the teachings of the invention without departing from theessential scope thereof. Therefore, it is intended that the inventionnot be limited to the particular embodiment(s) disclosed, but that theinvention will include all embodiments falling within the scope of theappended claims.

1. A monitoring system for measuring QT intervals in patients, themonitoring system comprising: a first monitoring device adhered to apatient at a first location that monitors a first electrocardiogram(EKG) signal associated with the patient; a QT interval measurementmodule configured to receive the first EKG signal from the firstmonitoring device, wherein the QT interval measurement module:identifies QRS complex attributes and heart rate attributes for eachbeat within the received first EKG signal, wherein QRS complexattributes include a peak of each QRS complex (iRpk) and a QRS onset(iRon); generates a T-wave offset estimate (iToff_estimate) based atleast in part on the identified heart rate attributes; identifies aT-wave offset detection window based on the identified QRS complex(iRpk) and the generated T-wave offset estimate (iToff_estimate);locates the T-wave offset (iToff) within the identified T-wave offsetdetection window based on detected maximums and minimums within theT-wave offset detection window; and measures QT intervals based onidentified QRS onset (iRon) and T-wave offset (iToff).
 2. The monitoringsystem of claim 1, wherein the QT interval measurement module identifiesbeats that are noisy and identifies a beat segment as non-noisy if aconsecutive number of beats are identified as non-noisy, wherein onlynon-noisy beat segments are utilized to measure QT interval.
 3. Themonitoring system of claim 1, wherein the QT interval measurement moduleselects a beat segment for QT interval analysis based on one or more oftime of day, activity level of the patient, orientation of the patient,and/or heart rate of the patient.
 4. The monitoring system of claim 1,wherein the QT interval measurement module discards beats in which QRSonset (iRon) and/or T-wave offset (iToff) cannot be discerned within thefirst EKG signal even if the beat is non-noisy.
 5. The monitoring systemof claim 1, wherein the T-wave offset detection window extends from theT-wave offset estimate (iToff_estimate) plus a threshold.
 6. Themonitoring system of claim 1, wherein locating the T-wave offsetestimate (iToff_estimate) for each beat includes utilizing theidentified heart rate attributes of the patient and a look-up table toestimate a T-wave offset window in which to search for the T-wave offset(iToff).
 7. The monitoring system of claim 1, wherein the QT intervalmeasurement module is located in an intermediate device that includes aprocessor for executing instructions stored in a computer readablemedium, and an antenna for receiving the first EKG signal from the firstmonitoring device.
 8. The monitoring system of claim 1, wherein the QTinterval measurement module generates an alert in response to detectedlong QT intervals.
 9. The monitoring system of claim 8, wherein the QTinterval measurement module provides generated alerts and the receivedfirst EKG signal to a remote monitoring center.
 10. A method ofdetecting QT intervals in patients, the method comprising: receiving anelectrocardiogram (EKG) signal monitored with respect to a patient;identifying QRS complex attributes and heart rate attributes for eachbeat within the received EKG signal, wherein QRS complex attributesinclude a peak of each QRS complex (iRpk) and a QRS onset (iRon);generating a T-wave offset estimate (iToff_estimate) based at least inpart on the identified heart rate attributes; identifying a T-waveoffset detection window based on the identified QRS complex (iRpk) andthe generated T-wave offset estimate (iToff_estimate); locating theT-wave offset (iToff) within the identified T-wave offset detectionwindow based on detected maximums and minimums within the T-wave offsetdetection window; and measuring QT intervals based on identified QRSonset (iRon) and T-wave offset (iToff).
 11. The method of claim 10,further including identifying beats that are noisy within the receivedEKG signal and setting beat-wise noise flags with respect to those beatsthat are noisy.
 12. The method of claim 11, further includingidentifying qualified beat segments within the EKG signal, wherein aqualified beat segment has a threshold number of consecutive non-noisybeats.
 13. The method of claim 12, wherein QT intervals are measuredwith respect to qualified beat segments.
 14. The method of claim 10,wherein a long QT syndrome flag is set in response to the measured QTinterval exceeding a threshold value.
 15. The method of claim 10,wherein the QT interval is stored and utilized as a benchmark forcomparison to subsequently measured QT intervals.